Analogues of Artificial Human Box C/D Small Nucleolar RNA As Regulators of Alternative Splicing 
of a pre-mRNA Target

• Published in: Actanaturae 2012-01, Vol.4 (1), p.32-41
• Main Authors: Stepanov, G A, Semenov, D V, Kuligina, E V, Koval, O A, Rabinov, I V, Kit, Y Y, Richter, V A
• Format: Article
• Language: English
• ISSN: 2075-8251
• DOI: 10.32607/20758251-2012-4-1-32-41

Small nucleolar RNAs (snoRNAs) play a key role in ribosomal RNA (rRNA) biogenesis. Box C/D snoRNAs guide the site-specific 2'-O-ribose methylation of nucleotides in rRNAs and small nuclear RNAs (snRNAs). A number of box C/D snoRNAs and their fragments have recently been reported to regulate post-transcriptional modifications and the alternative splicing of pre-mRNA. Artificial analogues of U24 snoRNAs directed to nucleotides in 28S and 18S rRNAs, as well as pre-mRNAs and mature mRNAs of human heat shock cognate protein (hsc70), were designed and synthesized in this study. It was found that after the transfection of MCF-7 human cells with artificial box C/D RNAs in complex with lipofectamine, snoRNA analogues penetrated into cells and accumulated in the cytoplasm and nucleus. It was demonstrated that the transfection of cultured human cells with artificial box C/D snoRNA targeted to pre-mRNAs induce partial splicing impairments. It was found that transfection with artificial snoRNAs directed to 18S and 28S rRNA nucleotides, significant for ribosome functioning, induce a decrease in MCF-7 cell viability.